Chemically induced tumors in skin and subcutaneous tissues have been determined to be clonal growths. It is important to the understanding of tumor biology to know if tumors in general arise from single cells (i.e. from rare events) and moreover if those phenomenon which appear to contribute to the formation of tumors, so called preneoplasias behave as if they are clonal growths. The method proposed is to construct chimeric rats (rats whose adult tissues are mosaics of the two strains used, ACI and Fisher) between strains of rat which vary in expression of major histocompatibility antigens. Antisera generated against RT-1 (histocompatibility) antigens will be fluorescenated. Direct immunofluorescence of frozen sections of the chimeric liver will form the basis of the marker system. Chimeras will be formed by morula fusion using available techniques. The chimeras will be treated with a single dose of diethylnitrosamine and partial hepatectomy followed by continued feeding of a diet containing 0.05 percent phenobarbital. Three months and six months after the beginning of the feeding, animals will be sacrificed. Serial frozen sections will be made and stained for either gamma-glutamyl transpetidase, adenosine triphosphatase, glucose-6-phosphatase or immunofluorescence. Alternate sections will be stained with hematoxylin and eosin. Enzyme altered areas and morphologically altered areas will be mapped using a digitizer and compared with the alternate fluorescein anti-RT1 stained sections. This will allow the origin of the cells (Fisher RT-1a or ACI RT-1 1) comprising the altered areas to be determined. If these areas are comprised entirely of cells derived from Fisher or from ACI, then one may conclude that they arose from a very small number of cells. Conversely, if the altered areas contain both Fisher and ACI derived cells, then one may conclude that they arose from a large number of cells.